The objective of the proposed research is to elucidate the mechanisms by which certain polyribonucleotides inhibit the growth of cancer cells. This objective is being approached by studying the biophysical basis of cultured cells and macrophage-polynucleotide interaction and by assessment of direct, indirect and selective cytotoxicity. Polycationic amino-acids have been used to potentiate polynucleotide uptake. It appears that the three main variables which mediate RNA uptake are (1) the nature of the surface of the recipient cell, (2) the type of polyamino acid used to potentiate uptake and (3) the bases present in the polynucleotide. The relative importance of these three parameters is being assessed as is the relation of the uptake process to cytotoxicity. Cytotoxicity is being studied (a) by following the direct effects of polynucleotides on the viability and proliferative capacity of target cells and (b) on indirect effects, specifically the stimulation of macrophages by polynucleotides to kill target cells. These binding and cytotoxicity studies may indicate ways whereby polynucleotide effects against cancer cells may be potentiated.